TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters.
TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters.
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DOI：
10.1093/nar/gkj400
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发表时间：
2006
影响因子：
14.9
通讯作者：
Chiariotti, L
中科院分区：
文献类型：
--
作者：
Angrisano, T;Lembo, F;Pero, R;Natale, F;Fusco, A;Avvedimento, VE;Bruni, CB;Chiariotti, L
我们最近报道了一种新型 MBD2 相互作用子 (MBDin)，即使在没有去甲基化事件的情况下，也能够重新激活 MBD2 抑制的甲基化启动子的转录。在这里，我们发现另一种不相关的蛋白质 TACC3 对甲基化基因表现出类似的活性。此外，这里报告的数据为所观察到的现象提供了可能的分子机制。免疫沉淀实验表明MBD2/TACC3在体内与组蛋白乙酰转移酶pCAF形成复合物。 MBD2 还可能与 HDAC2（MeCP1 抑制复合物的一个组成部分）相关联。然而，我们发现MBD2与TACC3/pCAF以及与HDAC2形成的复合物是相互排斥的。此外，HAT 酶测定表明，HAT 活性与体内 MBD2 相关，并且当 TACC3 过表达时，这种关联显着增加。总体而言，我们的研究结果表明，TACC3 可以被 MBD2 在甲基化启动子上招募，并且能够通过有利于包含 HAT 的 MBD2 复合物的形成来重新激活转录，从而甚至在最终去甲基化之前就将 MBD2 的抑制潜力转换为激活状态。
We have recently reported that a novel MBD2 interactor (MBDin) has the capacity to reactivate transcription from MBD2-repressed methylated promoters even in the absence of demethylation events. Here we show that another unrelated protein, TACC3, displays a similar activity on methylated genes. In addition the data reported here provide possible molecular mechanisms for the observed phenomenon. Immunoprecipitation experiments showed that MBD2/TACC3 form a complex in vivo with the histone acetyltransferase pCAF. MBD2 could also associate with HDAC2, a component of MeCP1 repression complex. However, we found that the complexes formed by MBD2 with TACC3/pCAF and with HDAC2 were mutually exclusive. Moreover, HAT enzymatic assays demonstrated that HAT activity associates with MBD2 in vivo and that such association significantly increased when TACC3 was over-expressed. Overall our findings suggest that TACC3 can be recruited by MBD2 on methylated promoters and is able to reactivate transcription possibly by favoring the formation of an HAT-containing MBD2 complex and, thus, switching the repression potential of MBD2 in activation even prior to eventual demethylation.
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影响因子：
10.5
作者：
Hendrich, B;Guy, J;Bird, A
通讯作者：
Bird, A
影响因子：
4.8
作者：
Sekimata, M;Takahashi, A;Homma, Y
通讯作者：
Homma, Y
影响因子：
3.4
作者：
Still, IH;Vettaikkorumakankauv, AK;Liang, P
通讯作者：
Liang, P
影响因子：
16
作者：
Hutchins, AS;Mullen, AC;Reiner, SL
通讯作者：
Reiner, SL
DOI：
10.1073/pnas.77.6.3455
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMBESIIMPIOMBATO, FS;PARKS, LAM;COON, HG
通讯作者：
COON, HG